A couple of nights ago, I was at a “journal club” discussion with several of my thoracic surgery colleagues and some others in the Seattle area who treat lung cancer, discussing how to decide which patients presenting with a solitary brain metastasis could have a realistic chance of being treated with curative intent in the chest as well as the brain. The idea behind this concept is that, while metastatic disease is generally recognized as a state that is binary (you have metastatic disease or you don’t) and isn’t curable if cancer has spread from the chest to another part of the body through bloodstream, it’s not always that simple.
There are exceptions to almost every rule, and we know that a minority of patients (perhaps as high as one in four) with a solitary brain or adrenal metastasis as their only evidence of metastatic spread can be treated aggressively in the chest, have their brain or adrenal metastasis treated locally (resected or possibly radiated), and be alive with no evidence of disease years later. We also know that having earlier stage lung cancer, discounting the single metastasis, is associated with a much better probability of doing very well. Specifically, the concept of treating metastatic lung cancer for cure tends to be most feasible for node-negative disease in the chest, but not for people who have nodal involvement, and especially not locally advanced, stage III NSCLC. In this situation, the metastasis probably isn’t “precocious”: it’s just a metastases coming in when you’d expect to see it.
So that’s the concept of the precocious metastasis. What I started thinking about was how this question can really be broadened to other situations in lung cancer, or other cancers, that really center on one key question:
Is it likely that one area of the cancer is so far ahead of the rest of the disease process that it will set the pace for problems, or is it more likely that the pace of the disease will be set by multiple disease areas?
And with this question in mind, we can apply this to many disease settings that essentially hinge on this question. For instance, this often comes up with technically multifocal bronchioloalveolar carcinoma (BAC), but with one dominant area, and now is the relevant question for the situation of whether to consider a local therapy in the setting of acquired resistance to a targeted therapy, or any other setting of very limited progression.
To illustrate the point about BAC, we know that many patients with BAC have a process that is technically multifocal, or at least suggestive of that, but who might arguably benefit from a local therapy, commonly surgery. Specifically, a patient often presents with a biopsy-confirmed are of growing BAC or adeno/BAC that is resectable, but we also see several tiny nodules measuring 2-3 mm scattered in the lungs. Does it make sense to treat with surgery, suspecting that this is actually a multifocal process?
To illustrate another common scenario, a patient with advanced NSCLC with lung and bone metastases has an activating EGFR mutation and demonstrates a terrific response to an EGFR tyrosine kinase inhibitor (TKI) that lasts for 16 months. A scan then shows a suggestion of one lung lesion growing, and treatment is continued without change, with another CT 8 weeks later showing that this one nodule is growing, now more quickly, against a background of otherwise ongoing great response. Dr. Weiss just wrote a great post about the concept of pursuing radiation for the area of progression and continuing the EGFR inhibitor.
In both of these cases, I would argue that even if you know that someone has metastatic disease, local therapy makes sense in any situation in which progression in one area is likely to far outpace the rest of the disease process. On the other hand, if the cancer is progressing visibly in multiple areas between scans a few months apart, that strongly suggests that treating with local therapy isn’t going to be helpful. Even treating all of those spots won’t likely help, because we can anticipate that new spots invisible on the current scan will be present on the next.
I’ll also say that while the concept of the precocious metastasis is framed around the idea that the goal of treatment is cure, I don’t think that the feasibility of cure needs to be the acid test to concluding whether local therapy is appropriate. Just like giving brain radiation to someone with multifocal brain metastases, the goal can be to address the most survival-limiting (and/or quality of life-limiting) aspect of the disease. We would readily favor adding a local therapy that can prolong survival by 6 or 12 months or longer, so while cure may be goal in a best-case scenario, falling short of that doesn’t obviate the value of local therapy.
I welcome your thoughts here. Do people see other cancer care scenarios in which this main question centers on “is the pace set by a local or systemic process?”.
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